1. Field of the Invention
The present invention describes a novel composition comprising a nonsteroidal antiinflammatory drug, their salts, their chirally pure forms, isomers and derivatives, analogues and adducts thereof and two drugs pitofenone hydrochloride and fenpiverinium bromide in a pharmaceutically acceptable combination for use in mammals particularly human beings.
2. Description of the Background
Amongst the various non-steroidal antiinflammatory drugs diclofenac particularly sodium diclofenac is widely used in the treatment of rheumatoid arthritis, osteoarthirities and ankylosing spondylitis. This has been disclosed in the following references (references from U.S. Pat. No. 5,202,159).
As such, intestinal, ureteric and biliary colic are extremely common clinical conditions requiring prompt medical attention to relieve the symptoms and help the patient get back to his/her vocation to avoid/minimize economic loss and reduce the load on the medical institution. Non surgical treatment can provide immediate relief to the patient while investigations are being carried out to determine the future course of management. Currently available treatment modalities include anticholinergics like, atropine and its derivatives, ambutonium, glycopyrronium, isoperopamide, pripenzolate, etc. Combination therapy with analgin, pitofenone and fenpiverinium are also used. In addition, drugs such as meberverine valethamate bromide, clidinium are also used with.
All drugs do not provide predictably uniform results in all patients. All the drugs used in these conditions do carry some side effects. Anticholinergics produce dry mouth, tachycardia in some patients, are contraindicated in glaucoma and prostatic hypertrophy and other antispasmodic agents may cause drowsiness as a side effect. Analgin is implicated in causing bone marrow depression.
In the comprehensive review of a pharmacological properties of diclofenac (Brogden et al, Drugs 20;24-48 (1980) it has been reported to have anti inflammatory activity, analgesic activity and anti pyretic activity. Conventionally it has been used in clinical condition for rheumatic disorders. Recently it has been reported to be of use in painful non-rheumatic syndromes for example biliary colic, {Grossi et al. Current Therapeutic Research, volume 40, No. 5, (1986)} and acute renal colic {Garcia Alonso F. et al, Eur. J. Clin Pharmacol, 40, 543-546 (1991)}.
However it has been reported that diclofenac sodium intramuscular is more effective than narcotic analgesic like pethidine intramuscular in the management of acute renal colic and has fewer side effects. Based on the market survey among the various products available as antispasmodic one major product is composed of analgin with two spasmolytic agents that is pitofenone hydrochloride and fenpiverinium bromide.
No pharmacological composition has been reported in literature as well as no product is available where an non-steroidal anti-inflammatory drugs such diclofenac and nimesulide is employed in combination with spasmolytic agents.
Our findings as disclosed in this patent application indicate that NSAID including diclofenac and nimesulide when combined with fenpiverinium bromide and pitofenone hydrochloride forms an excellent antispasmodic composition. The inventors after expenditure of considerable time, mental faculties and careful experimentation have surprisingly found that diclofenac potentiates the antispasmodic action of pitofenone hydrochloride and fenpiverinium bromide several times. Further, the safety of the combination has been demonstrated in animal models. Thereafter the efficacy of this combination was established by conducting clinical trials in-human volunteers. The composition when given orally and parenterally is not only clinically effective but is superior to the existing therapeutic agents. It is superior in two ways one it has more effective action and second it has fewer side effects.
Accordingly, it is an object of the present invention to provide a novel antispasmodic composition comprising non-steroidal antiinflammatory drugs, their salts, their chirally pure forms, isomers and derivatives analogues and adducts thereof and pitofenone hydrochloride and fenpiverinium bromide.
It is a further objective of the present invention to provide a process for the manufacture of a novel anti-spasmodic composition comprising diclofenac and pitofenone hydrochloride and fenpiverinium bromide.
It is a further objective of the invention to provide a novel injectable delivery system for the anti-spasmodic composition.
It is a further objective of the invention to provide an antispasmodic composition which can be taken orally by way of a pediatric suspension, capsule/tablet.